骨缝牵引成骨动物模型的建立及应用

Establishment and Application of a Rabbit Model of Midsagittal Sutural Distraction Osteogenesis

目的建立兔颅骨矢状缝牵引成骨的动物实验模型,评价该模型的可行性,并探讨局部应用rhBMP-2对牵引成骨的作用。方法以微型牵引种植钉(Miniscrew implants,MSI)作支抗,镍钛弹簧为牵引力源,建立MSI兔颅骨矢状缝弹力牵引成骨模型。应用该牵引系统对11周龄的新西兰白兔作矢状缝牵引成骨。将动物随机分为实验组(牵引+rh BMP-2,n=7),对照组(单纯牵引,n=7)。牵引29天,于0、5、11、17、23及29 d,应用X线及Micro-CT评价骨缝牵开情况;第7、27天注射四环素,第17天注射钙黄绿素,作为术后荧光组织切片观察标记。观察动物对该牵引成骨系统的耐受性,比较各组骨缝牵开的距离,并观察矢状缝组织形态学变化,验证兔颅骨矢状缝牵引成骨模型的可行性。结果MSI弹力牵引系统成功率为86%,牵引成骨实验可顺利完成。对照组矢状缝牵开的距离大于实验组(D29),两组矢状缝牵开的距离随着牵引持续时间的增加而递增,但骨缝牵开呈现先快后慢的趋势。骨组织形态学显示,两组骨缝间均有新生骨组织形成,说明该牵引成骨模型既能有效牵开骨缝,也能诱导骨缝间成骨。而实验组骨缝间新生骨组织形成速度大于对照组。结论本实验采用自行研制的微型种植钉MSI弹力牵引系统,成功建立了兔矢状缝弹力牵引成骨模型。骨缝牵引过程中,局部应用rhBMP-2可促进骨缝成骨,但导致了骨缝融合。

Objective To establish a rabbit model of midsagittal sutural distraction osteogenesis for future experiments, to evaluate this rabbit model＇s feasibility and to explore the role of rh BMP-2 in subperiosteum to distraction osteogenesis.Methods Nickel-titanium open coil springs（50 g） and 3 mm long miniscrew implants（MSIs） were used for skeletal anchorage to establish a rabbit model of midsagittal sutural distraction osteogenesis. Fourteen New Zealand white rabbits, 11 weeks, were randomized into experimental group（traction ＋rh BMP-2, n =7） and control group（simple traction, n =7）.Controlled extraoral forces were used to expand rabbit midsagittal sutures（ n=14） for 29 days, X ray and Micro-CT were used to evaluate the open joint and measure the distance between MSI of each group on day 0, 5, 11, 17, 23, and 29; Tetracycline was injected on day 7, 27 and calcein was injected on day 17, as a biomarker for fluorescence tissue section postoperatively.The feasibility of this sagittal suture distraction osteogenesis rabbit model was explored by observing the tolerance of the rabbit distraction osteogenesis system, comparing each joint open distance and the sagittal suture tissue morphology. Results The total successful rate of the rabbit model of midsagittal sutural distraction osteogenesis was 86%. Controlled extraoral forces were successfully used on the sutural distraction model. The open distance of sagittal suture（D29） in control group was greater than in experimental group. The open distance of sagittal suture was increased with the duration of traction in the two groups, but the sutural separation rate presented a trend of fast before they are slow. New bone formation was observed in both experimental group and control group by histomorphormetric analyses, which demonstrated that the distraction osteogenesis model can not only distract the suture effectively, but also induce the osteogenesis between the suture. But the new bone formation in experimental group was faster. Conclusion The rabbit model of midsagittal sutural distraction osteogenesis can be rapidly established by nickel-titanium open coil springs and 3 mm long miniscrew implants（MSI）. Local application of rh BMP-2 can promote the osteogenesis but lead to the suture fusion during the process of distraction.